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Protein / target

Sphingomyelin phosphodiesterase

Encoded bySMPD1P17405Homo sapiensSwiss-Prot
UniProt: P17405Ensembl: ENSG00000166311HGNC: HGNC:11120NCBI Gene: 6609
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Acid sphingomyelin phosphodiesterase

Strongest disease association

Niemann-Pick disease

Via encoding gene SMPD1 · Genetic evidence · score 0.94

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Converts sphingomyelin to ceramide.

View complete UniProt function annotation

Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly (PubMed:20807762, PubMed:21098024, PubMed:9660788). However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (PubMed:12563314, PubMed:20530211, PubMed:20807762, PubMed:22573858, PubMed:9393854)

Subcellular location

LysosomeLipid dropletSecretedSecreted, extracellular space
Domains and Gene Ontology detail (38)

Domains & features

Saposin B-type

Gene Ontology

  • Cendolysosome
  • Cendosome
  • Cextracellular exosome
  • Cextracellular space
  • Clamellar body
  • Clipid droplet
  • Clysosomal lumen
  • Clysosome
  • Cplasma membrane
  • Facid sphingomyelin phosphodiesterase activity
  • Fhydrolase activity, acting on glycosyl bonds
  • Fphosphatidylcholine phospholipase C activity

631 aa · 70 kDa · 4 isoforms

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SMPD1

Gene-level evidence surfaced through the gene SMPD1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Niemann-Pick disease
0.94Well supported

Genetic evidence dominant · Open Targets 0.67

Genetic Diseases, Inborn
0.78Well supported

Genetic evidence dominant · Open Targets 0.47

Lysosomal Storage Diseases
0.64Moderately supported

Genetic evidence dominant · Open Targets 0.58

Parkinson's Disease
0.53Limited support

Pathway evidence dominant · Open Targets 0.55 · no direct causal or clinical evidence

Alzheimer's Disease
0.49Preliminary

Pathway evidence dominant · Open Targets 0.55 · no direct causal or clinical evidence

View evidence synthesis (5)
Niemann-Pick diseaseWell supported
0.94
agreement 0.80–1.00
Genetic94%Literature6%Genetic literaturedup

Open Targets aggregate 0.67 · 2 independent evidence families · 1 not counted as duplicate

Genetic Diseases, InbornWell supported
0.78
agreement 0.64–0.92
Genetic98%Literature2%

Open Targets aggregate 0.47 · 2 independent evidence families

Lysosomal Storage DiseasesModerately supported
0.64
agreement 0.52–0.76
Genetic55%Pathway42%Literature3%

Open Targets aggregate 0.58 · 3 independent evidence families

Parkinson's DiseaseLimited support
0.53
agreement 0.39–0.67
Pathway52%Animal model27%Literature21%

Open Targets aggregate 0.55 · 3 independent evidence families · no direct causal or clinical evidence

Alzheimer's DiseasePreliminary
0.49
agreement 0.35–0.63
Pathway58%Literature23%Animal model19%

Open Targets aggregate 0.55 · 3 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Niemann-Pick disease0.67
Lysosomal Storage Diseases0.58
Parkinson's Disease0.55
Alzheimer's Disease0.55
Neurodegenerative Diseases0.53
Multiple Sclerosis0.52
Genetic Diseases, Inborn0.47

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Structure with LigandSM · High-Quality LigandAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.21 cites

Choi BJ · Experimental & molecular medicine · 2024

Recent

Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.

Choi BJ · Experimental & molecular medicine · 2024

Europe PMC papers linked directly to this protein.